Pharmacotherapeutic Pain Pearls at the Junction of National Awareness

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L to R: Mena Raouf, PharmD Candidate 2016; Jeffrey Fudin, BS, PharmD, DAAPM, FCCP, FASHP; Daralyn A. Morgenson BS, PharmD; Jeffrey James Bettinger, PharmD Candidate 2017

At the crossroads of September’s National Pain Awareness Month finale and October’s American National Pharmacists Month  commencement, it seems like a perfect day to post a summary of pertinent therapeutic topics that were featured in Pharmacy Times last month.  In an effort to expose more young pharmacists to this important therapeutic and grossly underserved training area, student pharmacists and post-doctoral residents took on the exciting task of highlighting five important patient / clinician centered topics in an effort to educate our colleagues.

Here to summarize and commemorate this collaborative informational effort with his peers is Student Pharmacist Mena Raouf.

Mena Raouf has this to share…

We took the opportunity to write a weekly article on pain-related topics that were published on the Pharmacy Times website and hyperlinked herein. One hundred million American are living with chronic pain1, which is more than diabetes2, coronary heart disease3, stroke3, and cancer combined. 4 Topics were carefully chosen and overseen for accuracy and content by Dr. Fudin in an effort to benefit clinicians and patients alike.

Pain Awareness Month was first started in 2001 when American Chronic Pain Association (ACPA), led a coalition of organizations, to develop Partners for Understanding. 5 The Partners for Understanding consortium, spearheaded by ACPA, strived to improve awareness about chronic pain and reduce the stigma attached.5  Thereafter, September has been the National Pain Awareness month.

This is particularly timely considering the current climate of a presumed opioid epidemic, the recent CDC Guideline for Prescribing Opioids for Chronic Pain, and an apparent massacre of opioid accessibility.

We covered a variety of topics ranging from novel NSAIDs and comparison of Gabapentinoids to opioid dosing strategies, complications, and risk mitigation strategies.

Without further ado, let’s take a look back on the topics covered

Week 1: Pharmacist Assessment of Opioid Overdose Risk

Community pharmacists can identify patients at risk for opioid induced respiratory depression based on established risk factors and provide education on opioid overdose risk and increase public health awareness on the availability of a potentially lifesaving intervention, naloxone for in-home use. See RIOSORD (summary of Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression).  

Table 1: Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (RIOSORD)

Description Y/N Score
In the past 6 months, has the patient had a health care visit (outpatient, inpatient, or ED) involving:
Opioid dependence? 15
Chronic hepatitis or cirrhosis? 9
Bipolar disorder or schizophrenia? 7
Chronic pulmonary disease? (e.g., emphysema, chronic bronchitis, asthma, pneumoconiosis, asbestosis) 5
Chronic kidney disease with clinically significant renal impairment? 5
Active traumatic injury, excluding burns? (e.g., fracture, dislocation, contusion, laceration, wound) 4
Sleep apnea? 3
Does the patient consume:
An extended-release or long-acting (ER/LA) formulation of any prescription opioid or opioid with long and/or variable half-life? (e.g.,OxyContin, Oramorph-SR, methadone, fentanyl patch, levorphanol) 9
Methadone? (Methadone is a long-acting opioid, so also write Y for “ER/LA formulation”) 9
Oxycodone? (If it has an ER/LA formulation [e.g., OxyContin], also write Y for “ER/LA formulation”) 3
A prescription antidepressant? (e.g., fluoxetine, citalopram, venlafaxine, amitriptyline) 7
A prescription benzodiazepine? (e.g., diazepam, alprazolam) 4
Is the patient’s current maximum prescribed opioid dose:
>100 mg morphine equivalents per day? 16
50-100 mg morphine equivalents per day? 9
20-50 mg morphine equivalents per day? 5
In the past 6 months, has the patient:
Had 1 or more ED visits? 11
Been hospitalized for 1 or more days? 8
Total Score 115

Table 2: OIRD probability based on calculated risk index

Risk index (score) OIRD probability (%)
0-24 3
25-32 14
33-37 23
38-42 37
43-46 51
47-49 55
50-54 60
55-59 79
60-66 75
≥67 86

Week 2: Opioid Conversion: New Perspectives on Dosing Calculations

Therapeutic conversion of opioids necessitates an important skillset that is sorely lacking. Therefore, the practice requires prescribers and pharmacists to pay careful attention and use good clinical therapeutic judgment and common sense. It is the classic case of where science, mathematics, and experience intersect. Online “equianalgesic” opioid dosing calculators may have quite a disparate output in terms of equianalgesic dosing between and among opioids.  This article reviews different opioid conversion calculators and important considerations when converting patients from one opioid to another.

Week 3: Nano-Formulated NSAIDs: A New Dawn for Safe Use

Low-dose micronized NSAIDs have been developed using nanotechnology to reduce particle size to increase drug surface area and enhance absorption, thereby achieving comparable efficacy to conventional formulations at minimal doses with reduced adverse event risks. FDA-approved micronized NSAIDs currently include indomethacin (Tivorbex) and diclofenac (Zorvolex) for the treatment of mild-moderate pain in adults. Zorvolex received an additional FDA approval in August for osteoarthritis management.

Pharmacokinetic Parameters for Micronized NSAIDs Compared to Conventional Formulations Under Fasted Conditions


  Indomethacin Diclofenac Meloxicam 
Dose equivalency Micronized Conventional Micronized Conventional Micronized Conventional
Dose equivalency 40 mg 50 mg 35 mg 50 mg 10 mg 15 mg
Cmax (ng/mL) 3115±900 2759±936 1347±764 1316±577 1.25±0.25 1.29±0.42
Tmax  (hours) 1.25±0.60 1.97±0.81 0.59±0.20 0.80±0.50 2.0 (1.0-5.0) 4.0 (2.0-8.0)
 AUC (h*ng/mL) 6861±1585 9306±2234 1204±324 1493±388 29.2±11 40.9±11.7
T ½ (hours) 7.73±2.07 8.45±3.16 1.85±0.45 1.92±0.38 22.0±10.1 23.6±10.0

Week 4:
How Gabapentin Differs From Pregabalin

Pregabalin and gabapentin are very variable products commonly used for treatment of neuropathy. This article compares the pharmacokinetics (PK) and pharmacodynamics (PD) of pregabalin with various gabapentin formulations, and also covers conversion regimens. The article reviews algorithms from cohort study that evaluated different approaches to switching patients with peripheral neuropathy from one gabapentin formulation to others, and to pregabalin.

Week 5: Opioid-Induced Androgen Deficiency: Pharmacist Counseling Points

Opioid-induced androgen deficiency (OPIAD) is a common yet under diagnosed adverse effect of chronic opioid use, which could worsen pain, affect patients’ quality of life, and lead to further health complications. Pharmacists should be aware of the complication, be able to identify patients on opioids with symptoms hypogonadism, and recommend that they contact their health care provider.  This article reviews OPIAD mechanism, complications, and reviews incidence with different opioids.

As we conclude pain month let’s remember a few things.

Chronic pain remains a public health concern that impacts the daily lives many Americans and is projected to become more prevalent as the population continues to age. There are various conundrums ranging from efficacy, safety, abuse, and complications in pain management, which makes pain management often challenging. Whether in a clinical or community setting, pharmacists are at a central point of contact for patients and have the opportunity to educate them on all aspects of pain medication use.  Pharmacists have the responsibility of monitoring the patient’s 4A’s: Analgesia, Activities of daily living, Adverse events, and Aberrant drug behaviors.6

Patients living with pain deserve the compassionate and high quality care and it our duty to ensure the efficacy and safety of their medication regimen. The next time we encounter a patient with chronic pain, let’s remember the Pharmacist’s Oath, 3 points of which squarely apply7

  • I will consider the welfare of humanity and relief of human suffering my primary concerns.
  • I will apply my knowledge, experience, and skills to the best of my ability to assure optimal drug therapy outcomes for the patients I serve.
  • I will embrace and advocate change in the profession of pharmacy that improves patient care.Group

Short bios for each contributor are listed on their respective Pharmacy Times posts for September 2015. L to R: Mena Raouf, PharmD Candidate 2016; Jeffrey Fudin, BS, PharmD, DAAPM, FCCP, FASHP; Daralyn A. Morgenson BS, PharmD; Jeffrey James Bettinger, PharmD Candidate 2017.
Photo by Wendy (Uyen) Nguyen, PharmD Candidate 2016 (far right)

As always, comments are welcomed!



  1. Institute of Medicine Report from the Committee on Advancing Pain Research, Care, and Education: Relieving Pain in America, A Blueprint for Transforming Prevention, Care, Education and Research. The National Academies Press, 2011.
  2. American Diabetes Association.
  3. Heart Disease and Stroke Statistics—2011 Update: A Report From the American Heart Association. Circulation 2011, 123:e18-e209, page 20.
  4. American Cancer Society, Prevalence of Cancer:
  5. American Chronic Pain Association.
  6. Passik SD, Kirsh KL, Whitcomb L, et al. Monitoring outcomes during long-term opioid therapy for noncancer pain: results with the Pain Assessment and Documentation Tool. J Opioid Manag. 2005;1(5):257-266. –
  7. American Pharmacist Association. Oath of the Pharmacist.

1 thought on “Pharmacotherapeutic Pain Pearls at the Junction of National Awareness

  1. I want to thank Dr. Fudin and his team for their noble efforts to help front-line pharmacists in reducing the rate of opioid related deaths that many claim to provide prima-facie evidence for a goal of reducing the use of this particular class of analgesics.

    I do not wish to comment on the validity of that claim, nor of its destructive influence on the quality of life for many of the 100-million in America who live with intractable pain.

    I do wish to ask Dr. Fudin and colleagues to consider another factor in their model that includes a measure of opioid use history in the person who requires chronic opioid therapy (COT).

    Some of us who live with moderate to severe daily pain rely on poly-pharmacy including opioids and benzodiazepenes to enjoy a certain quality of life, whether that involves raising children, following a career, or performing daily activities that many take for granted.

    Some of the “old timers” who live with pain, a group that includes this writer, have used poly-pharmacy successfully for many years. Our history implies a few pertinent considerations about the the efficacy of our medical regimen, as well as our capacity to avoid the pitfalls of addiction.

    Of greater relevance to this discussion of OIRD, a long history of COT also demonstrates a change in CNS physiology. Through mechanisms not yet well understood, my central nervous systems has developed a classic tolerance to large doses of opioids and certain benzos, and the risk for OIRD in people like me is far less than that in the group of opiate naive patients and those patient groups with a brief history of COT and therefore a lower tolerance to the opioid metabolites.

    None of our models reflect this tolerance gradient against dose and time, nor do they reflect the dose/analgesia curves that are so essential to the quality of life of millions on COT for 10, 15, 20, or more years. Unfortunately, longitudinal studies of people with chronic pain maintained on COT for 15, 20 years or more are non-existent.

    We live in a time when the science of pharmacology has a great opportunity to improve the treatment of pain by studying the pharmacogenetics, PK, metabolism, and other opioid properties in this elderly generation of pain patients.

    The study of pharmacogenetics is one area with enormous potential for helping the treatment of people in pain. This science is relatively new to both patients and clinicians and is poorly understood. Patients mistrust genetic testing, believing that the analysis of their squamous cells will somehow end up in Big Brother’s database. Front-line clinicians struggle daily with business management of medicine, and the bottom line provides a formidable barrier to seeing the benefits genetic testing can add to their practice.

    Clinicians, pharmacists, and pain patients are partners in this quest to lower accidental death and addiction rates from these essential medications, but our job is not complete unless we also work to increase analgesic efficacy for all who suffer from moderate to severe pain.

    Knowing a poor CYP2D6 metabolizer from an ultra-rapid CYP2D6 metabolizer can help an enlightened clinician understand their patient’s pain medication preferences in terms of metabolic pathways, hopefully eliminating those demeaning confrontations involving preferences of oxy- over hydro- codone.

    Current classifications of pain — terminal/non-terminal or acute/chronic — may have some utility in the thinking of those who deliver medical care, but the people in pain within these groups present a single data point in a wide spectrum of neurological activity mediated by a particular dose of opioid analgesic.

    When we can treat that pain effectively, with a margin of safety calculated for each individual patient, we will be well on our way to winning the fight against pain.

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